Fever (also known as pyrexia[1] or a febrile response) is defined as a body temperature above the normal range due to an increase in the temperature regulatory set-point. There is not a single agreed upon upper limit for normal temperature with sources using values between 37.5 and 38.3 °C (99.5 and 100.9 °F).[1][2] The increase in set-point triggers increased muscle tone and causes a feeling of cold resulting in greater heat production and efforts to conserve heat. This results in an increase in body temperature. When the set-point temperature returns to normal a person feels hot and may begin to sweat.

A fever may be useful as a defense mechanism as the body's immune response can be strengthened at higher temperatures; however, there are arguments for and against the usefulness of fever, and the issue is controversial. With the exception of very high temperatures, treatment to reduce fever is often not necessary. Antipyretic medications such as ibuprofen or paracetamol can be effective at lowering the temperature, which may improve comfort.[4]

Fever is one of the most common medical signs. It differs from hyperthermia, in that hyperthermia is an increase in body temperature over the body's thermoregulatory set-point, due to excessive heat production or insufficient heat loss.[1]

Temperature under the arm (axillary) or in the ear (otic) is at or over 37.2 °C (99.0 °F)

In healthy adult men and women, the range of normal, healthy temperatures for oral temperature is 33.2–38.2 °C (91.8–100.8 °F), for rectal it is 34.4–37.8 °C (93.9–100.0 °F), for tympanic membrane (the ear drum) it is 35.4–37.8 °C (95.7–100.0 °F), and for axillary (the armpit) it is 35.5–37.0 °C (95.9–98.6 °F).[10] Harrison's textbook of internal medicine defines a fever as a morning oral temperature of >37.2 °C (>98.9 °F) or an afternoon oral temperature of >37.7 °C (>99.9 °F) while the normal daily temperature variation is typically 0.5 °C (0.9 °F).[11]

Normal body temperatures vary depending on many factors, including age, sex, time of day, ambient temperature, activity level, and more. A raised temperature is not always a fever. For example, the temperature of a healthy person rises when he or she exercises, but this is not considered a fever, as the set-point is normal. On the other hand, a "normal" temperature may be a fever, if it is unusually high for that person. For example, medically frail elderly people have a decreased ability to generate body heat, so a "normal" temperature of 37.3 °C (99.1 °F) may represent a clinically significant fever.

The pattern of temperature changes may occasionally hint at the diagnosis:

Continuous fever: Temperature remains above normal throughout the day and does not fluctuate more than 1 °C in 24 hours, e.g.lobar pneumonia, typhoid, urinary tract infection, brucellosis, or typhus. Typhoid fever may show a specific fever pattern (Wunderlich curve of typhoid fever), with a slow stepwise increase and a high plateau. (Drops due to fever-reducing drugs are excluded.)

Intermittent fever: The temperature elevation is present only for a certain period, later cycling back to normal, e.g.malaria, kala-azar, pyaemia, or septicemia. Following are its types [12]

Quotidian fever, with a periodicity of 24 hours, typical of Plasmodium falciparum or Plasmodium knowlesimalaria

Remittent fever: Temperature remains above normal throughout the day and fluctuates more than 1 °C in 24 hours, e.g., infective endocarditis.

Pel-Ebstein fever: A specific kind of fever associated with Hodgkin's lymphoma, being high for one week and low for the next week and so on. However, there is some debate as to whether this pattern truly exists.[13]

A neutropenic fever, also called febrile neutropenia, is a fever in the absence of normal immune system function. Because of the lack of infection-fighting neutrophils, a bacterial infection can spread rapidly; this fever is, therefore, usually considered to require urgent medical attention. This kind of fever is more commonly seen in people receiving immune-suppressing chemotherapy than in apparently healthy people.

Febricula is an old term for a low-grade fever, especially if the cause is unknown, no other symptoms are present, and the patient recovers fully in less than a week.[14]

Hyperthermia: Characterized on the left. Normal body temperature (thermoregulatory set point) is shown in green, while the hyperthermic temperature is shown in red. As can be seen, hyperthermia can be conceptualized as an increase above the thermoregulatory set point.Hypothermia: Characterized in the center: Normal body temperature is shown in green, while the hypothermic temperature is shown in blue. As can be seen, hypothermia can be conceptualized as a decrease below the thermoregulatory set point.Fever: Characterized on the right: Normal body temperature is shown in green. It reads "New Normal" because the thermoregulatory set point has risen. This has caused what was the normal body temperature (in blue) to be considered hypothermic.

Temperature is ultimately regulated in the hypothalamus. A trigger of the fever, called a pyrogen, causes a release of prostaglandin E2 (PGE2). PGE2 then in turn acts on the hypothalamus, which generates a systemic response back to the rest of the body, causing heat-creating effects to match a new temperature level.

In many respects, the hypothalamus works like a thermostat.[21] When the set point is raised, the body increases its temperature through both active generation of heat and retention of heat. Peripheral vasoconstriction both reduces heat loss through the skin and causes the person to feel cold. If these measures are insufficient to make the blood temperature in the brain match the new set point in the hypothalamus, then shivering begins in order to use muscle movements to produce more heat. When the hypothalamic set point moves back to baseline either spontaneously or with medication, the reverse of these processes (vasodilation, end of shivering and nonshivering heat production) and sweating are used to cool the body to the new, lower setting.

This contrasts with hyperthermia, in which the normal setting remains, and the body overheats through undesirable retention of excess heat or over-production of heat.[21] Hyperthermia is usually the result of an excessively hot environment (heat stroke) or an adverse reaction to drugs. Fever can be differentiated from hyperthermia by the circumstances surrounding it and its response to anti-pyretic medications.

One model for the mechanism of fever caused by exogenous pyrogens includes LPS, which is a cell wall component of gram-negative bacteria. An immunological protein called lipopolysaccharide-binding protein (LBP) binds to LPS. The LBP–LPS complex then binds to the CD14 receptor of a nearby macrophage. This binding results in the synthesis and release of various endogenous cytokine factors, such as interleukin 1 (IL-1), interleukin 6 (IL-6), and the tumor necrosis factor-alpha. In other words, exogenous factors cause release of endogenous factors, which, in turn, activate the arachidonic acid pathway.

PGE2 is the ultimate mediator of the febrile response. The set point temperature of the body will remain elevated until PGE2 is no longer present. PGE2 acts on neurons in the preoptic area (POA) through the prostaglandin E receptor 3 (EP3). EP3-expressing neurons in the POA innervate the dorsomedial hypothalamus (DMH), the rostral raphe pallidus nucleus in the medulla oblongata (rRPa), and the paraventricular nucleus (PVN) of the hypothalamus . Fever signals sent to the DMH and rRPa lead to stimulation of the sympathetic output system, which evokes non-shivering thermogenesis to produce body heat and skin vasoconstriction to decrease heat loss from the body surface. It is presumed that the innervation from the POA to the PVN mediates the neuroendocrine effects of fever through the pathway involving pituitary gland and various endocrine organs.

In infants, the autonomic nervous system may also activate brown adipose tissue to produce heat (non-exercise-associated thermogenesis, also known as non-shivering thermogenesis). Increased heart rate and vasoconstriction contribute to increased blood pressure in fever.

There are arguments for and against the usefulness of fever, and the issue is controversial.[24][25] There are studies using warm-bloodedvertebrates[26] and humans[27]in vivo, with some suggesting that they recover more rapidly from infections or critical illness due to fever. A Finnish study suggested reduced mortality in bacterial infections when fever was present.[28]

In theory, fever can aid in host defense.[24] There are certainly some important immunological reactions that are sped up by temperature, and some pathogens with strict temperature preferences could be hindered.[29]

Research[30] has demonstrated that fever assists the healing process in several important ways:

Fever should not necessarily be treated.[32] Most people recover without specific medical attention.[33] Although it is unpleasant, fever rarely rises to a dangerous level even if untreated. Damage to the brain generally does not occur until temperatures reach 42 °C (107.6 °F), and it is rare for an untreated fever to exceed 40.6 °C (105 °F).[32]

Some limited evidence supports sponging or bathing feverish children with tepid water.[34] The use of a fan or air conditioning may somewhat reduce the temperature and increase comfort. If the temperature reaches the extremely high level of hyperpyrexia, aggressive cooling is required.[16] In general, people are advised to keep adequately hydrated.[35] Whether increased fluid intake improves symptoms or shortens respiratory illnesses such as the common cold is not known.[36]

Medications that lower fevers are called antipyretics. The antipyretic ibuprofen is effective in reducing fevers in children.[37] It is more effective than acetaminophen (paracetamol) in children. Ibuprofen and acetaminophen may be safely used together in children with fevers.[38][39] The efficacy of acetaminophen by itself in children with fevers has been questioned.[40] Ibuprofen is also superior to aspirin in children with fevers.[41] Additionally, aspirin is not recommended in children and young adults (those under the age of 16 or 19 depending on the country) due to the risk of Reye's syndrome.[42]

Using both paracetamol and ibuprofen at the same time or alternating between the two is more effective at decreasing fever than using only paracetamol or ibuprofen.[43] It is not clear if it increases child comfort.[43]

A number of types of fever were known as early as 460 BC to 370 BC when Hippocrates was practicing medicine including that due to malaria (tertian or every 2 days and quartan or every 3 days).[45] It also became clear around this time that fevers were a symptom of a disease rather than a disease in and of itself.[45]

Fever phobia is the name given by medical experts to parents' misconceptions about fever in their children. Among them, many parents incorrectly believe that fever is a disease rather than a medical sign, that even low fevers are harmful, and that any temperature even briefly or slightly above the oversimplified "normal" number marked on a thermometer is a clinically significant fever.[46] They are also afraid of harmless side effects like febrile seizures and dramatically overestimate the likelihood of permanent damage from typical fevers.[46] The underlying problem, according to professor of pediatrics Barton D. Schmitt, is "as parents we tend to suspect that our children’s brains may melt."[47]

As a result of these misconceptions parents are anxious, give the child fever-reducing medicine when the temperature is technically normal or only slightly elevated, and interfere with the child's sleep to give the child more medicine.[46]

Fever is an important feature for the diagnosis of disease in domestic animals. The body temperature of animals, which is taken rectally, is different from one species to another. For example, a horse is said to have a fever above 101 °F (38.3 °C).[48] In species that allow the body to have a wide range of "normal" temperatures, such as camels,[49] it is sometimes difficult to determine a febrile stage.

Fever can also be behaviorally induced by invertebrates that do not have immune-system based fever. For instance, some species of grasshopper will thermoregulate to achieve body temperatures that are 2 - 5 °C higher than normal in order to inhibit the growth of fungal pathogens such as Beauveria bassiana and Metarhizium acridum.[50] Honeybee colonies are also able to induce a fever in response to a fungal parasite Ascosphaera apis. [50]